Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis.

Abstract

Dopamine supersensitivity occurs in schizophrenia and other psychoses, and after hippocampal lesions, antipsychotics, ethanol, amphetamine, phencyclidine, gene knockouts of Dbh (dopamine beta-hydroxylase), Drd4 receptors, Gprk6 (G protein-coupled receptor kinase 6), Comt (catechol-O-methyltransferase), or Th-/-, DbhTh/+ (tyrosine hydroxylase), and in rats born by Cesarean-section. The functional state of D2, or the high-affinity state for dopamine (D2High), was measured in these supersensitive animal brain striata. Increased levels and higher proportions (40-900%) for D2High were found in all these tissues. If many types of brain impairment cause dopamine behavioral supersensitivity and a common increase in D2High states, it suggests that there are many pathways to psychosis, any one of which can be disrupted.

• Authors: Philip Seeman, David Weinshenker, Remi Quirion, Lalit K Srivastava, Sanjeev K Bhardwaj, David K Grandy, Richard T Premont, Tatyana D Sotnikova, Patricia Boksa, Mufida El-Ghundi, Brian F O'dowd, Susan R George, Melissa L Perreault, Pekka T Männistö, Siobhan Robinson, Richard D Palmiter, Teresa Tallerico
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 102 Issue 9 Pg. 3513-8 (Mar 01 2005) ISSN: 0027-8424 [Print] United States
• PMID: 15716360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Drd4 protein, rat
• Receptors, Dopamine D2
• Receptors, G-Protein-Coupled
• Receptors, Dopamine D4
• Quinpirole
• Dopamine beta-Hydroxylase
• Catechol O-Methyltransferase
• Phencyclidine
• Dopamine

Topics

• Animals
• Catechol O-Methyltransferase (genetics, physiology)
• Corpus Striatum (physiopathology)
• Dopamine (physiology)
• Dopamine beta-Hydroxylase (genetics, physiology)
• Male
• Phencyclidine (pharmacology)
• Psychotic Disorders (etiology)
• Quinpirole (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Dopamine D2 (genetics, physiology)
• Receptors, Dopamine D4
• Receptors, G-Protein-Coupled (genetics, physiology)